FIGURE 4. Regulation of PDK4 expression by PGC-1α (Wende et al. 2005).
4.4 Long-term adaptations in energy metabolism during exercise
Regular endurance training results in improvement of aerobic capacity which is demonstrat-ed by increasdemonstrat-ed VO2max. This improvement is due to multiple adaptations in cardio-vascular system and skeletal muscle tissue induced by training. (Holloszy & Coyle 1984.) The cen-tral cardio-vascular adaptations are out of the scope of this literature review, and thus, adap-tations taking place in the peripheral tissues, especially skeletal muscle, are in the focus here.
It has been established that fat oxidation during submaximal exercise increases after en-durance training (Carter et al. 2001; Friedlander et al. 1998a; Holloszy & Coyle 1984; Hor-owitz & Klein 2000; Phillips et al. 1996). This effect is due to many adaptations taking place in skeletal muscle tissue: the delivery of fatty acids to muscle fibers is enhanced by increased capillarization in skeletal muscle tissue, the capacity to transport fatty acids into muscle fibers and mitochondria is increased when the expression of transport proteins in-creases and finally, the capacity to oxidize fatty acids is improved by increasing mitochon-drial density and enzyme activities in muscle fibers. (Holloszy & Coyle 1984; Horowitz &
Klein 2000; Kiens et al. 1993; Kiens et al. 1997; Talanian et al. 2007.)
The data obtained from previous research shows, that the increased fat oxidation isn’t relat-ed to increasrelat-ed lipolysis in adipose tissue. Endurance trainrelat-ed subjects have been found to have similar adipose tissue and whole-body lipolytic responses to epinephrine and to exer-cise at same absolute intensity, respectively, as untrained subjects. (Horowitz & Klein 2000;
Stallknecht et al. 1995.) However, trained subjects seemed to have enhanced epinephrine-stimulated adipose tissue blood flow (Stallknecht et al. 1995). During exercise at same rela-tive intensity, endurance trained subjects have higher whole-body lipolytic rates, which might result from increased delivery of epinephrine to adipose tissue by enhanced adipose tissue blood flow (Horowitz & Klein 2000). In addition, trained individuals may rely more on IMTGs as substrates, as previously untrained subjects have been found to have decreased plasma FFA turnover and oxidation after a 12-week endurance training period despite in-creased total fat oxidation during prolonged exercise (Horowitz & Klein 2000; Martin et al.
1993).
Contradictory findings exist, however. Friedlander et al. (1999) found that whole-body li-polysis and total fat oxidation were unaffected after 10-week endurance training but FFA rate of appearance (Ra) as well as rate of disappearance (Rd) were increased after training during exercise at both same absolute and same relative intensity in young men. In young women, 12-week but otherwise similar endurance training resulted in increased FFA rate of appearance, rate of disappearance and oxidation measured during exercise at same absolute
and relative intensities, whereas no change was found in whole-body lipolysis. The in-creased fat oxidation in women after training was mainly due to inin-creased plasma FFA oxi-dation. (Friedlander et al. 1998a) These results suggest that women may rely more on fat oxidation after endurance training than men (Friedlander et al. 1998a; Friedlander et al.
1999). It has been suggested that women rely more on fat oxidation than men during pro-longed moderate intensity exercise also before endurance training (Carter et al. 2001).
Consistent findings have been established for adaptations in CHO metabolism by the same group. Glucose flux (Ra, Rd and metabolic clearance rate, MCR) was decreased after endur-ance training period in both men and women during exercise at same absolute intensity, but not at same relative intensity. This suggests that glucose flux is related to relative exercise intensity. When it comes to glucose oxidation, it decreased during exercise at both same absolute and relative intensity in men, and only at same absolute intensity in women. In women, also the relative contribution of CHOs to total energy expenditure was decreased after training during exercise at both same absolute and relative intensity, whereas no signif-icant changes were found in men. These values were signifsignif-icantly different between gen-ders. (Friedlander et al. 1997; Friedlander et al. 1998b.) However, in all of these studies by Friedlander et al. (1997; 1998a; 1998b; 1999) the relative improvement in aerobic capacity (VO2peak) was approximately twice as great in women as in men, which might have had something to do with demonstrated gender differences in CHO and lipid metabolism.
In another study, as a consequence of seven weeks of endurance training the proportion of fat oxidized increased during exercise at same absolute intensity but not same relative inten-sity. This was also seen as lower RER values at same absolute but not at same relative in-tensity. Consistently, the relative contribution of CHOs to substrate oxidation decreased at same absolute but not at same relative intensity after training. However, glucose flux (Ra, Rd and MCR) was diminished during exercise at same absolute and same relative intensity, but glucose Ra and Rd were higher during exercise at same relative intensity than at same abso-lute intensity. Glucose uptake was diminished after training at both same absoabso-lute and same relative intensity. Glycerol Ra and Rd weren’t altered by training period. Plasma
norepineph-rine concentration was lower after training during exercise at same absolute intensity but not at same relative intensity. For men, plasma epinephrine concentration was lower after training during prolonged exercise at both same absolute and same relative intensity, while women showed lowered concentration only at same absolute intensity. Both men and wom-en improved their VO2peak similarly. (Carter et al. 2001.)
Already a short period of endurance training may induce changes in substrate utilization.
Phillips et al. (1996) found a 10% increase in fat oxidation due to increased IMTG and de-creased glycogen oxidation during exercise at same absolute intensity after only five days of endurance training. After 31 days of training fat oxidation during exercise was increased further with concomitant decrease in CHO oxidation. Total fat oxidation was increased by
~70% mainly due to increased oxidation of IMTGs, while the reduced CHO oxidation was predominantly due to decrease in the rate of glycogen oxidation. Catecholamine response to exercise at same absolute intensity was attenuated in trained state. VO2peak was improved after 30 days of training (10%) but wasn’t significantly changed after only eight days of training. (Phillips et al. 1996.)
Contrary to the previously presented results, it has been also suggested that increased fat oxidation during exercise at same absolute intensity after training would result from in-creased uptake of FFAs into muscle cells due to enhanced transport capacity rather than from increased oxidation of IMTGs. This enhanced capacity for FFA uptake was suggested to be due to either increased capillarization or metabolic changes in trained skeletal muscle that improve the capacity to oxidize FFAs, demonstrated by increased activities of enzymes β-HAD and citrate synthase. It was also concluded that hormones, such as insulin and cate-cholamines, are not likely to play as important role in the shift of substrate use as the adap-tations at the level of trained muscle. (Kiens et al. 1993.)
Also two weeks of high-intensity interval training (HIIT) has been found to increase VO2peak
and whole-body fat oxidation and to decrease reliance on muscle glycogen during exercise at 60% of pre-training VO2peak in women. Similarly to more conventional endurance
train-ing, HIIT resulted in increased maximal activities of β-HAD and citrate synthase and in increased protein content of total muscle plasma membrane fatty acid-binding protein (FABPpm). No changes were found in fatty acid translocase (FAT)/CD36 or cytosolic HSL content. These results suggest increased capacity to transport and oxidize FFAs during exer-cise after HIIT. (Talanian et al. 2007.) Increase in skeletal muscle FABPpm after more con-ventional endurance training has also been reported earlier (Kiens et al. 1997).
Contrary to previously presented results, Tunstall et al. (2002) demonstrated that nine days of endurance training increased the expression of FAT/CD36 both at mRNA and protein levels, without any changes in FABPpm expression. Also CPT1 mRNA expression was in-creased as a consequence of training suggesting, that the expression of genes related to FFA transport across plasma and mitochondrial membranes could play a role in increased fat oxidation in trained state. However, the mRNA expression of PPARγ was decreased after training, whereas no changes were found in the expression of PPARα, PGC-1α or SREBP-1c, all of which are transcriptional regulators of genes related to fatty acid uptake and oxida-tion. The expression of none of these factors was changed acutely in response to a single exercise bout. (Tunstall et al. 2002.) These gene expression results are somewhat contradic-tory to other studies as for example skeletal muscle PPARα protein expression has been found to increase substantially after 12 weeks of endurance training and it has even been suggested to play a regulatory role in increased fat oxidation after training (Horowitz et al.
2000). The interpretation of the results of Tunstall et al. (2002) is limited by the lack of pro-tein expression data, small number of subjects and relatively short training period.
Some discrepancies exist between the results of different studies concerning for example the mechanism and the source of increased fat oxidation, or substrate kinetics during exercise at same absolute and same relative intensity. In some studies increased oxidation of IMTGs has been suggested to be the reason for increased fat oxidation while others suggest that it is due to increased plasma FFA oxidation. Similarly, some results suggest increased FFA transport capacity while others rather increased capacity to metabolize FFAs. The reasons for these differences are not known, but some of them may be at least partially explained by
slightly different exercise intensities used in trials, different exercise training modes or some other differences in the experimental protocols or methods that were used. (Carter et al. 2001; Friedlander et al. 1998a; Horowitz et al. 2000; Kiens et al. 1993; Phillips et al.
1996; Tunstall et al. 2002.)